The first synthesis of substituted azepanes mimicking monosaccharides: a new class of potent glycosidase inhibitors
The synthesis of the first examples of seven-membered ring iminoalditols, molecules displaying an extra hydroxymethyl substituent on their seven-membered ring compared to the previously reported polyhydroxylated azepanes, has been achieved from D-arabinose in 10 steps using RCM of a protected N-allyl-aminohexenitol as a key step. While the (2R, 3R, 4R)-2-hydroxymethyl-3,4-dihydroxy-azepane 10, a seven-membered ring analogue of fagomine, is a weak inhibitor of glycosidases, the (2R, 3R, 4R, 5S, 6S)-2-hydroxymethyl-3,4,5,6-tetrahydroxy-azepane 9 selectively inhibits green coffee bean alpha-galactosidase in the low micromolar range (Ki = 2.2 muM) despite a D-gluco relative configuration.
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Keywords: Ring-closing metathesis ; 7-membered iminocyclitols ; therapeutic ; applications ; xanthocercis-zambesiaca ; advanced malignancies ; biological evaluation ; expeditious synthesis ; branched cyclitols ; sugar ; mimetics ; imino sugars
Ecole Normale Super, Dept Chim, UMR 8642, F-75231 Paris 05, France. Ecole Polytech Fed Lausanne, BCH, Inst Sci & Ingn Chim, CH-1015 Lausanne, Switzerland. CSIC, Ctr Invest Biol, E-28040 Madrid, Spain.
Record created on 2005-11-09, modified on 2016-08-08